Vial and method for producing the same

ABSTRACT

A method for producing a vial with low alkali elution by removing a deteriorated region caused by processing on an internal surface of a vial is disclosed. The method is for forming vials from borosilicate glass tubes with a bottom wherein an internal surface of the tube is fire-blasted with a flame.

This application is a Divisional of co-pending application Ser. No.11/920,425 filed on Nov. 15, 2007 and for which priority is claimedunder 35 U.S.C §120. Application Ser. No. 11/920,425 is the nationalphase of PCT International Application No. PCT/JP2006/309674 filed onMay 15, 2006. PCT International Application No. PCT/JP2006/309674 claimsthe benefit of priority to JP-2005-226042, filed on Aug. 3, 2005 andJP-2005-143307, filed on May 16, 2005. The entire content of all of theabove applications is hereby incorporated by reference.

TECHNICAL FIELD

The present invention relates to a vial with low alkali elution and amethod for producing the same.

BACKGROUND ART

Automatic vial-forming machines forming vials from borosilicate glasstubes include a vertical type and a horizontal type. In both cases,vials are produced by first forming a mouth of a vial and then forming abottom of the vial. Chemical quality of the resultant vials areevaluated by a value of eluted alkali measured by Method 2 (internalsurface method) defined in the Japanese Pharmacopoeia or a testingmethod in conformity with the same. To obtain vials with low alkalielution, it is general practice to perform a process operated at lowtemperatures for a long time, away from use of a process operated athigh temperatures for a short time.

However, even if the vials are produced by the low-temperature process,they have a deteriorated region caused by processing in the form of abelt on the internal surface close to the bottom of the vial, which hasproblems such as, for example, alkali elution affecting pharmaceuticalproducts contained therein. This deterioration caused by processing isconsidered to be a phenomenon such that alkali-containing materialsexuded from or vaporized from the glass are condensed to a plurality ofsmall droplets and deposited on the internal surface of the vial in theprocess of forming the vial bottom from the borosilicate glass tube.

In order to lower or prevent elution of alkali from the condenseddroplets on the internal surface of the vial, some processes have beenproposed that include a method (S method) of allowing the alkali in thedeteriorated region to react with sulphate ions at the final stage ofvial forming process, and then washing the vial with water to removealkali as sodium sulphate (Na₂SO₄); and a method of covering theinternal surface of the vial with a thin film of silica (SiO₂) bychemical vapor deposition (CVD) to prevent elution of alkali. However,the S method requires an increased cost form washing the vial to removewhite sodium sulphate produced on the internal surface of the vial andthe internal surface after alkali extraction has a markedly unevencratered surface. On the other hand, the method of covering the internalsurface of the vial with the silica thin film results in increasedprocessing cost.

-   Patent document 1: JP H06-45481B-   Patent document 2: JP H06-76233B-   Patent document 3: JP 3,268,470

DISCLOSURE OF INVENTION Problems to be Solved by the Invention

Accordingly, a first issue to be solved is the deteriorated regionproduced by processing on the internal surface of the vial, and a secondissue is the removal of the deteriorated region produced by processing.It is therefore an object of the present invention to provide a vialwith low alkali elution and a method for producing the same.

Means for Solving the Problems

A main feature of the present invention is to minimize the formation ofa deteriorated region produced by processing on an internal surface of avial in a process of forming vials from borosilicate glass tubes by thesteps of forming a bottom first and then forming a mouth. The mostdistinguishing feature of the present invention is that the methodcomprises the steps of forming a bottom, subsequently removing theproduced deteriorated region by fire blasting with an oxygen-fire flame,and then forming a mouth.

According to the present invention, there is provided a method forproducing vials with low alkali elution by forming vials fromborosilicate glass tubes, said method comprising a first step of forminga borosilicate glass tube into a cup-shaped body to form a bottom of avial; and a second step of forming a mouth of said cup-shaped body tocomplete a vial with reduced alkali elution. Also provided is a methodfor producing vials with low alkali elution by forming vials fromborosilicate glass tubes, said method comprising a first step of forminga borosilicate glass tube into a cup-shaped body to form a bottom of avial; a second step of fire-blasting an internal surface of saidcup-shaped body by a certain length from the bottom toward an opening ofsaid cup-shaped body with flames to remove a deteriorated region causedby processing; and a third step of forming a mouth of said cup-shapedbody to complete a vial with reduced alkali elution. Further provided isa method for producing vials with low alkali elution by forming vialsfrom borosilicate glass tubes, said method comprising: a first step offorming a mouth of a vial; a second step of forming a bottom of thevial; and a third step of fire-blasting an internal surface of the vialfrom the bottom toward an opening of said cup-shaped body by a certainlength with flames to remove the deteriorated region caused byprocessing to complete a vial with reduced alkali elution.

According to the present invention, there is further provided a vialproduced by forming a borosilicate glass tube, characterized in thatsaid vial is reduced in alkali elution by a procedure comprising a firststep of forming a borosilicate glass tube into a cup-shaped body to forma bottom of a vial; and a second step of forming a mouth of saidcup-shaped body.

Also provided is a vial produced by forming a borosilicate glass tube,characterized in that said vial is reduced in alkali elution by aprocedure comprising: a first step of forming a borosilicate glass tubeinto a cup-shaped body to form a bottom of a vial; a second step offire-blasting an internal surface of said cup-shaped body from thebottom toward the opening of said cup-shaped body by a certain distancewith flames to remove a deteriorated region caused by forming; and athird step of forming a mouth of said cup-shaped body to complete a vialwith reduced alkali elution.

Further provided is a vial produced by forming a borosilicate glasstube, characterized in that said vial is reduced in alkali elution by aprocedure comprising: a first step of forming a borosilicate glass tubeto form a mouth of a vial; a second step of forming the resultant glasstube to form a bottom of the vial; and a third step of fire-blasting aninternal surface of the vial from the bottom toward the opening of saidcup-shaped body by a certain distance with flames to remove adeteriorated region caused by forming, thereby completing the vial withreduced alkali elution.

In addition, the aforesaid flames are gas-and-oxygen flames produced bya point burner. Further, the aforesaid fire-blasting is carried outwhile rotating the vial.

Effects of the Invention

In the conventional automated forming process of forming vials fromborosilicate glass tubes, the vial is produced by forming its mouth atthe start and then forming its bottom. In the process of forming thebottom, a number of small droplets containing alkali (Na₂O) exuded orvaporized from the glass are deposited on the internal surface of thevial to produce a deteriorated region caused by processing, which causesalkali elution.

In contrast thereto, when the borosilicate glass tube is formed into acup-shaped container only by formation of a bottom, the alkali elutiontest showed that an amount of alkali eluted from the cup-shapedcontainer is reduced to one-fifth to one-sixth of that of the vialformed by the conventional process comprising the steps of forming amouth first and forming a bottom. Further, an internal surface of theabove cup-shaped body is subjected to fire-blasting by means of anoxygen-gas flame from a point burner, so that the deteriorated regioncaused by processing can be completely removed from the container.According to the present invention therefore it is possible to obtainvials of which a deteriorated region caused by processing has beenminimized or removed from the deteriorated region caused by processing.

BRIEF DESCRIPTION OF DRAWINGS

FIG. 1 is an electron microscope photograph of a deteriorated regionaffected by processing of a cup C according to the present invention,and

FIG. 2 is an electron microscope photograph showing a deterioratedregion affected by processing of a cup C according to the presentinvention.

BEST MODE FOR CARRYING OUT THE INVENTION

The inventors have found that, when the forming steps in the process offorming borosilicate glass tube into a vial are carried out in the orderof bottom-forming to mouth-forming, the quantity of eluted alkali isreduced to one-fifth to one-sixth of that of the vial formed by theconventional process proceeding from mouth-forming to bottom-forming. Inthe conventional process proceeding from mouth forming to bottomforming, alkali-containing materials exuded from or vaporized from theglass at the time of bottom forming are trapped in the vial-in-processbecause of a narrowed mouth of the vial-in-process, resulting information of the deteriorated region due to processing. In contrast, inthe process proceeding from bottom forming to mouth forming, it isbelieved that the vaporized materials are easily released from thevial-in-process to the outside because of a large opening of thevial-in-process, resulting in decrease in formation of the deterioratedregion due to processing, which in turn causes lowering of the alkalielution. When the borosilicate glass is intensely heated by anoxygen-gas flame of the point burner, the flame changes from an earlyblue flame to a yellow flame with increasing temperature. This resultsfrom the flame reaction of sodium (Na) present in the glass. Based onthese observations, the inventors have found that use of fire-blastingwith a sharp and strong oxygen-gas flame makes it possible to remove thedeteriorated region induced by processing in the internal surface of thevial. It is believed that the fire-blasting is shot-blasting withparticle ions and molecules in the flame.

In order to remove the processing-induced deteriorated region byfire-blasting, it is required to allow the oxygen-gas flame jet from thepoint burner to flow out with little resistance after impingement on theinner surface of the glass tube. To this end, the vial forming processis required to begin with forming of a bottom to make a glass tube intoa cup-shaped body and then proceed to forming of a mouth. It should benoted that the quantity of eluted alkali for evaluation of effects ofthe forming process according to the present invention was determined asan amount (mL) of 0.01 mol/L sulfuric acid consumed in accordance withMethod 2 (internal surface method) defined in the JapanesePharmacopoeia.

EXAMPLE 1

Using the conventional process (mouth-forming to bottom-formingprocess), there were produced vials with 60 mm-height×12.5 mm-internalmouth diameter (Vial P) from borosilicate glass tubes with a 30 mm-outerdiameter and a 1.5 mm-thickness. The quantity of eluted alkali measuredfor “vial P” was 0.74 mL.

Separate from the above, the same glass tubes were formed intocup-shaped containers (cup A) by forming a bottom with an automaticvertical forming machine. The quantity of eluted alkali measured for“cup A” was 0.10 mL. Using a horizontal forming machine, “cup A” wasprovided with a mouth to form it into a vial (vial Q) in accordance withthe forming process of the present invention (bottom-forming tomouth-forming process). The quantity of eluted alkali measured for “vial0” was also 0.10 mL and there was no change in alkali elution caused bythe mouth-forming process. It is believed that this results from thefact that the processing temperature of the mouth-forming is lower thanthat of the bottom-forming and causes low volatilization of thealkali-containing material.

TABLE 1 outer diameter × inner Eluted height × diameter of alkali Samplethickness (mm) mouth (mm) (mL) Vial P 30 × 60 × 1.5 12.5 0.74(mouth-forming −> bottom-forming) Cup A same as above 27.0 0.10 Vial Qsame as above 12.5 0.10 (bottom-forming−> mouth-forming)

EXAMPLE 2

A borosilicate glass tube with a length of 200 mm was closed at one endthereof with a silicone rubber stopper, held vertically, and the filledwith a volume of water and autoclaved at 121° C. for 60 minutes. Thequantity of eluted alkali per 100 mL was 0.03 mL. This value wasregarded as the quantity of eluted alkali for the vial never affected byprocessing.

Samples (cup B) were formed from the “cup A” in Example 1 byfire-blasting an internal surface of the “cup A” about 10 mm above itsbottom with an obliquely-directed oxygen-gas flame about 10 cm long,while holding and rotating the “cup A”. The quantity of eluted alkalimeasured for “cup B” was 0.03 mL. It is believed that this results fromthe fact that the deteriorated region due to processing is removed bythe fire-blasting, thereby recovering the original surface of theborosilicate glass tubes. The fire-blasting was done using a pointburner with a 1.0 mm bore diameter which is fed by mixed gas of 0.75L/min town gas (methane) and 2.20 L/min oxygen to generate an about 10cm long flame.

Then, the “cup B” was provided with a mouth by a horizontal formingmachine to form it into a vial (vial R), of which the quantity of elutedalkali was 0.03 mL. As mentioned in Example 1, It is believed that thisresults from the fact that the processing temperature of themouth-forming is lower than that of the bottom-forming, thus making itharder for the alkali-containing material to volatilize.

TABLE 2 outer diameter × bore Eluted height × diameter alkali Samplethickness (mm) (mm) (mL) borosilicate 30 × 60 × 1.5 27.0 0.03 glass tubeCup A same as above 27.0 0.10 Cup B same as above 27.0 0.03(fire-blasting treatment) Vial R same as above 12.5 0.03 (Cup B −>mouth-forming)

EXAMPLE 3

Borosilicate glass tubes with a 40.5 mm-outer diameter and a 1.5mm-thickness were formed into vials with 78.5 mm-height×22.0 mm-internalmouth diameter by the conventional process (mouth-forming tobottom-forming). The quantity of eluted alkali measured for the vial was0.57 mL. Using the automatic vertical forming machine, a glass tube wasprovided with a bottom to prepare a cup-shaped container (cup C). Thequantity of eluted alkali measured for cup C was 0.21 mL. The quantityof eluted alkali measured for cup D prepared by fire-blasting aninternal surface of the “cup C” was 0.03 mL. The quantity of elutedalkali measured for a vial made from the cup D by provision of a mouthwith the horizontal forming machine was 0.03 mL.

TABLE 3 outer diameter × bore Eluted height × diameter alkali Samplethickness (mm) (mm) (mL) Vial S 40.5 × 78.5 × 1.5 22.0 0.57(mouth-forming−> bottom-forming) Cup C same as above 37.5 0.21 Cup Dsame as above 37.5 0.03 (fire-blasting treatment) Vial T same as above22.0 0.03 (Cup D −> mouth-forming)

Electron microscopic observation on the “cup C” showed that there is adeteriorated region due to processing, which has a crater-like patternresulting from alkali-containing volatiles (a photograph of FIG. 1). Onthe other hand, electron microscopic observation of the cup D, preparedby fire-blasting the deteriorated region due to processing of “cup C”,showed that the region corresponding to the deteriorated region due toprocessing has no crater-like pattern (photograph of FIG. 2). This showsthat the deteriorated region due to processing was removed byfire-blasting.

EXAMPLE 4

Borosilicate glass tubes with a 40.5 mm-outer diameter and a 1.5mm-thickness were formed into vials with 78.5 mm-height×22.0 mm-internalmouth diameter by the conventional process (mouth-forming tobottom-forming). The quantity of eluted alkali measured for theresultant vial was 0.57 mL. Using the point burner which generates agas-oxygen mixed gas flame (about 10 cm long), the resultant vials weresubjected to fire blasting so that the flame is blasted to thedeteriorated region about 10 mm above the bottom while rotating thevial. The vial subjected to the fire-blasting for 40 seconds showed thatthe quantity of eluted alkali was reduced to 0.30 mL, while vialsubjected to the fire-blasting for 60 seconds showed that the quantityof eluted alkali was reduced to 0.13 mL. The vials after thefire-blasting treatment possess no change in both shape and size. It isto be noted that the fire-blasting time (seconds) which has an effect ondecrease of alkali elution can be shortened by preheating of the vials.From these results, it was confirmed that the deteriorated region of thevials caused by the conventional forming process can be substantiallyremoved by fire-blasting.

TABLE 4 Outer diameter × bore Eluted height × diameter alkali Samplethickness (mm) (mm) (mL) Vial S 40.5 × 78.5 × 1.5 22.0 0.57(mouth-forming−> bottom-forming) Vial T same as above 22.0 0.30 (fireblasting) (40 seconds) Vial U same as above 22.0 0.13 (fire blasting)(60 seconds)

The invention claimed is:
 1. A method for treating a borosilicate glasstube with a closed end wherein an internal surface of the tube isfire-blasted with a flame.
 2. The method according to claim 1, whereinthe tube has a deteriorated region caused by processing on the internalsurface, which is removed by said fire-blasting.
 3. The method accordingto claim 1 wherein the internal surface is fire-blasted from the closedend to an opening of the tube.
 4. The method according to claim 2wherein the internal surface is fire-blasted from the closed end to anopening of the tube.
 5. The method according to claim 1 wherein saidflame is a gas-and-oxygen flame produced by a point burner.
 6. Themethod according to claim 2 wherein said flame is a gas-and-oxygen flameproduced by a point burner.
 7. The method according to claim 3 whereinsaid flame is a gas-and-oxygen flame produced by a point burner.
 8. Themethod according to claim 4 wherein said flame is a gas-and-oxygen flameproduced by a point burner.
 9. The method according to claim 1 whereinthe internal surface of the tube is fire-blasted with the flame whilerotating the tube.
 10. The method according to claim 2 wherein theinternal surface of the tube is fire-blasted with the flame whilerotating the tube.
 11. The method according to claim 3 wherein theinternal surface of the tube is fire-blasted with the flame whilerotating the tube.
 12. The method according to claim 4 wherein theinternal surface of the tube is fire-blasted with the flame whilerotating the tube.
 13. The method according to claim 5 wherein theinternal surface of the tube is fire-blasted with the flame whilerotating the tube.
 14. The method according to claim 6 wherein theinternal surface of the tube is fire-blasted with the flame whilerotating the tube.
 15. The method according to claim 7 wherein theinternal surface of the tube is fire-blasted with the flame whilerotating the tube.
 16. The method according to claim 8 wherein theinternal surface of the tube is fire-blasted with the flame whilerotating the tube.
 17. The method according to claim 1, wherein saidflame is jetted from a point burner to flow out with little resistanceafter impingement on the internal surface of the glass tube.